Relpax

"Migraine medications overview

Migraine is a serious, potentially life-threatening neurological disease that affects nearly 32 million Americans, the majority of whom are women. The hallmark symptom of migraine is an escalating, often "...

WARNINGS

PRECAUTIONS

RELPAX should only be usedwhere a clear diagnosis of migraine has been established.

Myocardial Ischemia, Myocardial
Infarction, and Prinzmetal's Angina

RELPAX is contraindicated in
patients with ischemic or vasospastic CAD. There have been rare reports of
serious cardiac adverse reactions, including acute myocardial infarction,
occurring within a few hours following administration of RELPAX. Some of these
reactions occurred in patients without known CAD. RELPAX may cause coronary
artery vasospasm (Prinzmetal's angina), even in patients without a history of
CAD.

Perform a cardiovascular
evaluation in triptan-na´ve patients who have multiple cardiovascular risk
factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong
family history of CAD) prior to receiving RELPAX. Do not use RELPAX if there is
evidence of CAD or coronary artery vasospasm [see CONTRAINDICATIONS]. For
patients with multiple cardiovascular risk factors who have a negative
cardiovascular evaluation, consider administering the first RELPAX dose in a
medically-supervised setting and performing an electrocardiogram (ECG)
immediately following administration of RELPAX. For such patients, consider
periodic cardiovascular evaluation in intermittent long-term users of RELPAX.

Arrhythmias

Life-threatening disturbances
of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following
the administration of 5-HT1 agonists. Discontinue RELPAX if these disturbances
occur. RELPAX is contraindicated in patients with Wolff-Parkinson-White
syndrome or arrhythmias associated with other cardiac accessory conduction
pathway disorders [see CONTRAINDICATIONS].

Chest, Throat, Neck and/or Jaw
Pain/Tightness/Pressure

Sensations of tightness, pain,
and pressure in the chest, throat, neck, and jaw commonly occur after treatment
with RELPAX and are usually non-cardiac in origin. However, perform a cardiac
evaluation if these patients are at high cardiac risk. RELPAX is contraindicated
in patients with CAD or Prinzmetal's variant angina [see CONTRAINDICATIONS].

Cerebrovascular Events

Cerebralhemorrhage,
subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1
agonists, and some have resulted in fatalities. In a number of cases, it
appears possible that the cerebrovascular events were primary, the 5-HT1 agonist
having been administered in the incorrect belief that the symptoms experienced
were a consequence of migraine, when they were not.

Before treating headaches in
patients not previously diagnosed as migraineurs, and in migraineurs who
present with symptoms atypical of migraine, other potentially serious
neurological conditions need to be excluded. RELPAX is contraindicated in
patients with a history of stroke or TIA [see CONTRAINDICATIONS].

Other Vasospasm Reactions

RELPAX may cause non-coronary
vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal
vascular ischemia and infarction (presenting with abdominal pain and bloody
diarrhea), and Raynaud's syndrome. In patients who experience symptoms or signs
suggestive of a vasospastic reaction following the use of any 5-HT1 agonist,
rule out a vasospastic reaction before receiving additional RELPAX doses [see CONTRAINDICATIONS].

Medication Overuse Headache

Overuse of acute migraine drugs
(e.g. ergotamine, triptans, opioids, or combination of these drugs for 10 or
more days per month) may lead to exacerbation of headache (medication overuse
headache). Medication overuse headache may present as migraine-like daily
headaches or as a marked increase in frequency of migraine attacks.
Detoxification of patients, including withdrawal of the overused acute migraine
drugs and treatment of withdrawal symptoms (which often includes a transient
worsening of headache) may be necessary.

Increase in Blood Pressure

Significant elevation in blood
pressure, including hypertensive crisis with acute impairment of organ systems,
has been reported on rare occasions in patients treated with 5-HT1 agonists,
including patients without a history of hypertension. Monitor blood pressure in
patients treated with RELPAX. RELPAX is contraindicated in patients with
uncontrolled hypertension [see CONTRAINDICATIONS].

Anaphylactic/Anaphylactoid
Reactions

There have been reports of
anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema
in patients receiving RELPAX. Such reactions can be life threatening or fatal.
In general, anaphylactic reactions to drugs are more likely to occur in
individuals with a history of sensitivity to multiple allergens. RELPAX is
contraindicated in patients with a history of hypersensitivity reaction to
RELPAX [see CONTRAINDICATIONS].

Patient Counseling Information

Inform patients that RELPAX may
cause serious cardiovascular adverse reactions such as myocardial infarction or
stroke, which may result in hospitalization and even death. Although serious
cardiovascular reactions can occur without warning symptoms, instruct patients
to be alert for the signs and symptoms of chest pain, shortness of breath,
weakness, slurring of speech, and instruct them to ask for medical advice when
observing any indicative sign or symptoms. Instruct patients to seek medical
advice if they have symptoms of other vasospastic reactions [see WARNINGS
AND PRECAUTIONS].

Anaphylactic/Anaphylactoid
Reactions

Inform patients that
anaphylactic/anaphylactoid reactions have occurred in patients receiving
RELPAX. Such reactions can be life threatening or fatal. In genera l, anaphylactic
reactions to drugs are more likely to occur in individuals with a history of sensitivity
to multiple allergens [see CONTRAINDICATIONS].

Medication Overuse Headache

Inform patients that use of
drugs to treat acute migraines for 10 or more days per month may lead to an
exacerbation of headache, and encourage patients to record headache frequency
and drug use (e.g., by keeping a headache diary) [see WARNINGS AND
PRECAUTIONS].

Serotonin Syndrome

Inform patients about the risk
of serotonin syndrome with the use of RELPAX or other triptans, particularly
during combined use with selective serotonin reuptake inhibitors (SSRIs) or
serotonin norepinephrine reuptake inhibitors (SNRIs) [see WARNINGS
AND PRECAUTIONS and DRUG INTERACTIONS].

Pregnancy

Inform patients that RELPAX
should not be used during pregnancy unless the potential benefit justifies the
potential risk to the fetus [see Use In Specific Populations].

Nursing Mothers

Inform patients to notify their
healthcare provider if they are breastfeeding or plan to breastfeed [see Use
in Specific Populations].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis,
Impairment of Fertility

Carcinogenesis

Eletriptan was administered to
rats and mice in the diet for 104 weeks. In rats, the incidence of testicular
interstitial cell adenomas was increased at the high dose of 75 mg/kg/day, but
not at 15 mg/kg/day, a dose associated with plasma exposures (AUC)
approximately 2 times that in humans at the MRHD of 80 mg/day. In mice, the
incidence of hepatocellular adenomas was increased at the high dose of 400
mg/kg/day, but not a dose of 90 mg/kg/day, associated with plasma AUC
approximately 7 times that in humans at the MRHD.

Impairment of Fertility

In a fertility and early
embryonic development study, eletriptan (50, 100, or 200 mg/kg/day) was orally
administered to male and female rats prior to and throughout mating and
continuing in females to implantation. Plasma exposures (AUC) were 4, 8 and 16
times in males and 7, 14 and 28 times in females, respectively, that in humans
at the MRHD. Dose-related decreases in the number of corpora lutea, implants,
and viable fetuses per dam were observed at all doses. Prolongation of the
estrus cycle was observed at the highest dose tested. Male fertility parameters
were not affected.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in
pregnant women. In reproductive toxicity studies in pregnant animals, oral
administration of eletriptan was associated with developmental toxicity
(decreased fetal and pup weights and an increased incidence of fetal structural
abnormalities) at clinically relevant plasma exposures. RELPAX should be used
during pregnancy only if the potential benefit justifies the potential risk to
the fetus

When pregnant rats were administered eletriptan during
the period of organogenesis at doses of 10, 30 or 100 mg/kg/day, fetal weights
were decreased and the incidences of vertebral and sternebral variations were
increased at 100 mg/kg/day (approximately 12 times the maximum recommended
human dose [MRHD] of 80 mg/day on a mg/m² basis). The 30 and 100 mg/kg/day doses were also
maternally toxic, as evidenced by decreased maternal body weight gain during
gestation. The no-effect dose for developmental toxicity in rats was 30
mg/kg/day, which is approximately 4 times the MRHD on a mg/m² basis.

When doses of 5, 10, or 50 mg/kg/day were given to
pregnant rabbits throughout organogenesis, fetal weights were decreased at 50
mg/kg/day, which is approximately 12 times the MRHD on a mg/m² basis. The incidences of fused
sternebrae and vena cava deviations were increased at all doses. Maternal
toxicity was not evident at any dose. A no-effect dose for developmental
toxicity in rabbits was not established; the lowest dose tested (5 mg/kg/day)
is similar to the MRHD on a mg/m² basis.

Nursing Mothers

Eletriptan is excreted in human milk. Caution should be
exercised when RELPAX is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not
been established.

The efficacy of RELPAX Tablets (40 mg) in patients 11-17
was not established in a randomized, placebo-controlled trial of 274 adolescent
migraineurs [see Clinical Studies]. Adverse reactions observed were
similar in nature to those reported in clinical trials in adults. Postmarketing
experience with other triptans includes a limited number of reports that
describe pediatric patients who have experienced clinically serious adverse
reactions that are similar in nature to those reported rarely in adults.
Long-term safety of eletriptan was studied in 76 adolescent patients who
received treatment for up to one year. A similar profile of adverse reactions to
that of adults was observed. The long-term safety of eletriptan in pediatric
patients has not been established.

Geriatric Use

Blood pressure was increased to a greater extent in
elderly subjects than in young subjects. The pharmacokinetic disposition of
eletriptan in the elderly is similar to that seen in younger adults [see CLINICAL
PHARMACOLOGY]. In clinical trials, there were no apparent differences in
efficacy or the incidence of adverse reactions between patients under 65 years
of age and those 65 and above.